FR901228 in Treating Patients With Relapsed or Refractory Advanced Ovarian Epithelial Cancer

The University of Chicago

Status and phase: Withdrawn; Phase 2

Conditions: Ovarian Cancer

Treatments: Drug: depsipeptide

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00085527

12965A

NCI-6347

LUMC-106995

UCCRC-12965

Details and patient eligibility

About

RATIONALE: FR901228 may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

PURPOSE: This phase II trial is studying how well FR901228 works in treating patients with relapsed or refractory advanced ovarian epithelial cancer.

Full description

OBJECTIVES:

Primary

• Determine the response rate (complete and partial) in patients with relapsed or refractory advanced ovarian epithelial carcinoma treated with FR901228 (depsipeptide).
• Determine the toxicity of this drug in these patients.

Secondary

• Correlate clinical response with platinum sensitivity in patients treated with this drug.
• Correlate clinical response with P-glycoprotein expression or p53 status in patients treated with this drug.

OUTLINE: This is multicenter study. Patients are stratified according to response to prior platinum administration (platinum resistant vs platinum sensitive).

Patients receive FR901228 (depsipeptide) IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 20-37 patients will be accrued for this study within 12 months.

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed ovarian epithelial carcinoma

  • Advanced disease

• Relapsed after OR refractory to 1, and only 1, prior platinum- or taxane-based regimen

  • Refractory disease defined as disease progression during platinum- or taxane-based therapy

  • Relapsed disease defined as platinum or taxane resistant or sensitive

    • Platinum or taxane resistance defined as relapse within 6 months after prior platinum or taxane therapy
    • Platinum or taxane sensitivity defined as relapse > 6 months from the last platinum or taxane treatment

• Measurable or evaluable disease

  • Measurable disease defined as at least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
  • Evaluable disease determined by elevation in CA 125 (≥ 2 times upper limit of normal [ULN]), ascites, or pleural effusion

• No known brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• SWOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• At least 24 weeks

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• WBC ≥ 3,000/mm^3

Hepatic

• AST and ALT ≤ 2.5 times ULN
• Bilirubin normal

Renal

• Creatinine normal OR
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• QTc < 500 msec
• LVEF > 40% by MUGA
• No significant cardiac disease
• No symptomatic congestive heart failure
• No unstable or poorly controlled angina pectoris
• No uncontrolled dysrhythmias
• No New York Heart Association class III or IV congestive heart failure
• No myocardial infarction within the past year
• No prior serious ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row)
• No left ventricular hypertrophy by EKG

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Potassium ≥ 4.0 mmol/L
• Magnesium ≥ 2.0 mg/dL
• No prior allergic reaction attributed to compounds of similar chemical or biological composition to FR901228 (depsipeptide)
• No concurrent uncontrolled illness
• No active or ongoing infection
• No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent biologic agents

Chemotherapy

• See Disease Characteristics
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• No prior FR901228 (depsipeptide)
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• More than 4 weeks since prior radiotherapy and recovered
• No concurrent radiotherapy

Surgery

• Prior surgical resection allowed

Other

• No concurrent drugs known to have HDI activity (e.g., sodium valproate)
• No concurrent agents that cause QTc prolongation
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent hydrochlorothiazide
• No other concurrent investigational agents
• No other concurrent anticancer therapy

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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0 participants in 1 patient group

depsipeptide

Experimental group

Description:

Depsipeptide administered on Days 1, 8, and15 of a 28-day cycle.

Treatment:

Drug: depsipeptide